More than 50% of human immunodeficiency virus type 1 (HIV-1) infected individuals experience neurological and psychiatric problems that are collectively termed the AIDS Dementia Complex (ADC). The current global AIDS crisis highlights the need for therapeutic strategies to treat ADC. A wealth of experimental data has implicated glycoprotein gpl20, an HIV-derived envelope protein that facilitates viral entry into cells, in the cell death associated with ADC. Clinical observations of ADC patients, in vitro characterization of cell types vulnerable to gp 120 neurotoxicity, and preliminary in vivo data in our laboratory suggest that basal ganglia dysfunction, especially of the nigro-striatal pathway, is integral to the neurological manifestations in ADC. Neurotrophic factors are naturally occurring proteins that are essential for brain development and maintenance of neuronal populations affected in ADC. The proposed experiments will examine the hypothesis that gp 120 causes cell death in the basal ganglia and that neurotrophic factors can protect against gp 120-mediated cell death. This neuroprotection in turn may limit neurological complications associated with HIV infection in the brain. [unreadable] [unreadable] [unreadable]